The American journal of tropical medicine and hygiene, Jan 10, 2015
We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA... more We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women ...
In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be... more In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral we...
Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From Dece... more Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From December 2010 through March 2014, hospital-based encephalitis surveillance in Bangladesh identified 18 clusters of NiV infection. The source of infection for case-patients in 3 clusters in 2 districts was unknown. A team of epidemiologists and anthropologists investigated these 3 clusters comprising 14 case-patients, 8 of whom died. Among the 14 case-patients, 8 drank fermented date palm sap (tari) regularly before their illness, and 6 provided care to a person infected with NiV. The process of preparing date palm trees for tari production was similar to the process of collecting date palm sap for fresh consumption. Bat excreta was reportedly found inside pots used to make tari. These findings suggest that drinking tari is a potential pathway of NiV transmission. Interventions that prevent bat access to date palm sap might prevent tari-associated NiV infection.
To determine whether 2 readily available indicators predicted survival among patients with Ebola ... more To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations.
The American journal of tropical medicine and hygiene, Jan 10, 2015
We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA... more We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women ...
In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prev... more In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prevention established a field laboratory in Sierra Leone in response to the ongoing Ebola virus outbreak. Through March 2015, this laboratory tested >12 000 specimens from throughout Sierra Leone. We describe the organization and procedures of the laboratory located in Bo, Sierra Leone.
Rapid, reliable and easy to use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are u... more Rapid, reliable and easy to use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the percentage agreement among Emergency Use Authorization (EUA) tests for the detection of ZEBOV nucleic acid including the BioFire FilmArray® BioThreat (BT) panel, the FilmArray BT E-panel and the NP2 and VP40 quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole blood, plasma and urine clinical specimens from persons diagnosed with Ebola virus disease (EVD). The percentage agreement for FilmArray and qRT-PCR assays using contrived whole blood specimens was 100% (6/6) for each ZEBOV dilution from 4x10(7)-4x10(2) virus/ml as well as the no-virus negative control. The limit of detection for FilmArray and qRT-PCR based on duplicate positive results was determined to be 4x10(2) inactivated ZEBOV/ml. Percentage agreement between FilmArray and qRT-PCR using clinical specimens from patients with EVD was 85% (23/27) when testing whole blood, 90%(18/20) when testing whole blood by FilmArray and matched plasma by qRT-PCR and 85% (11/13) when testing urine. Of 60 specimens, eight discordant results were noted with ZEBOV nucleic acid detected only by FilmArray in four specimens and only by qRT-PCR in the remaining four. These findings demonstrate that the rapid and easy to use FilmArray panels are effective tests for evaluating patients with EVD.
The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (... more The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 22, 2015
The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals b... more The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
Proceedings of the National Academy of Sciences, 2015
Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity t... more Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.
We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in c... more We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.
We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in c... more We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.
The American journal of tropical medicine and hygiene, Jan 10, 2015
We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA... more We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women ...
In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be... more In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral we...
Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From Dece... more Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From December 2010 through March 2014, hospital-based encephalitis surveillance in Bangladesh identified 18 clusters of NiV infection. The source of infection for case-patients in 3 clusters in 2 districts was unknown. A team of epidemiologists and anthropologists investigated these 3 clusters comprising 14 case-patients, 8 of whom died. Among the 14 case-patients, 8 drank fermented date palm sap (tari) regularly before their illness, and 6 provided care to a person infected with NiV. The process of preparing date palm trees for tari production was similar to the process of collecting date palm sap for fresh consumption. Bat excreta was reportedly found inside pots used to make tari. These findings suggest that drinking tari is a potential pathway of NiV transmission. Interventions that prevent bat access to date palm sap might prevent tari-associated NiV infection.
To determine whether 2 readily available indicators predicted survival among patients with Ebola ... more To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations.
The American journal of tropical medicine and hygiene, Jan 10, 2015
We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA... more We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women ...
In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prev... more In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prevention established a field laboratory in Sierra Leone in response to the ongoing Ebola virus outbreak. Through March 2015, this laboratory tested >12 000 specimens from throughout Sierra Leone. We describe the organization and procedures of the laboratory located in Bo, Sierra Leone.
Rapid, reliable and easy to use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are u... more Rapid, reliable and easy to use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the percentage agreement among Emergency Use Authorization (EUA) tests for the detection of ZEBOV nucleic acid including the BioFire FilmArray® BioThreat (BT) panel, the FilmArray BT E-panel and the NP2 and VP40 quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole blood, plasma and urine clinical specimens from persons diagnosed with Ebola virus disease (EVD). The percentage agreement for FilmArray and qRT-PCR assays using contrived whole blood specimens was 100% (6/6) for each ZEBOV dilution from 4x10(7)-4x10(2) virus/ml as well as the no-virus negative control. The limit of detection for FilmArray and qRT-PCR based on duplicate positive results was determined to be 4x10(2) inactivated ZEBOV/ml. Percentage agreement between FilmArray and qRT-PCR using clinical specimens from patients with EVD was 85% (23/27) when testing whole blood, 90%(18/20) when testing whole blood by FilmArray and matched plasma by qRT-PCR and 85% (11/13) when testing urine. Of 60 specimens, eight discordant results were noted with ZEBOV nucleic acid detected only by FilmArray in four specimens and only by qRT-PCR in the remaining four. These findings demonstrate that the rapid and easy to use FilmArray panels are effective tests for evaluating patients with EVD.
The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (... more The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 22, 2015
The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals b... more The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
Proceedings of the National Academy of Sciences, 2015
Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity t... more Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.
We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in c... more We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.
We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in c... more We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.
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Papers by Shelley M Brown